Biomedical subjects

Gang Hu

Publications and source records attributed to Gang Hu.

At least 19 recordsLinked to original sources

PubMed2006

EGFR-mediated expression of aquaporin-3 is involved in human skin fibroblast migration.

AQP3 (aquaporin-3), known as an integral membrane channel in epidermal keratinocytes, facilitates water and glycerol movement into and out of the skin. Here, we demonstrate that AQP3 is also expressed in cultured human skin fibroblasts, which under normal wound healing processes migrate from surrounding tissues to close the wound. EGF (epidermal growth factor), which induced fibroblast migration, also induced AQP3 expression in a time- and dose-dependent manner. CuSO4 and NiCl2, previously known as AQP3 water transport inhibitors, as well as two other bivalent heavy metals Mn2+ and Co2+, inhibited EGF-induced cell migration in human skin fibroblasts. AQP3 knockdown by small interfering RNA inhibited EGF-induced AQP3 expression and cell migration. Furthermore, an EGFR (EGF receptor) kinase inhibitor, PD153035, blocked EGF-induced AQP3 expression and cell migration. MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase]/ERK inhibitor U0126 and PI3K (phosphoinositide 3-kinase) inhibitor LY294002 also inhibited EGF-induced AQP3 expression and cell migration. Collectively, our findings show for the first time that AQP3 is expressed in human skin fibroblasts and that EGF induces AQP3 expression via EGFR, PI3K and ERK signal transduction pathways. We have provided evidence for a novel role of AQP3 in human skin fibroblast cell migration, which occurs during normal wound healing.

Aquaporin 3↗

PubMed2006

Expression and colocalization of NADPH-diaphorase and Fos in the subnuclei of the parabrachial nucleus in rats following visceral noxious stimulation.

To investigate whether neural nitric oxide synthase (nNOS) in the parabrachial nucleus (PB) is involved in processing visceral noxious stimulation, we mapped the distribution of histochemical staining for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), a marker for nNOS, and immunohistochemical staining for Fos, a neuronal activity marker, in the subnuclei of the PB following 2% formalin injection into the stomach of rats. NADPH-d and noxious-stimuli induced Fos staining were also examined in tissue containing PB cells labeled by the retrograde transport of fluogold (FG) injected into the central nucleus of the amygdala (CeA). We found that the number of Fos immunoreactive (Fos-IR) neurons was significantly increased in the dorsal lateral (dl), external lateral (el) and Kölliker-Fuse (KF) subnuclei of the PB. We observed that intensely labeled (type 1) NADPH-d positive neurons were mainly located in the rostral part of the PB; they extended long processes adjacent Fos-IR neurons, but no Fos/type 1 NADPH-d double-labeled neurons were seen. In contrast, lightly labeled (type 2) NADPH-d positive neurons were principally localized in the dl of the PB, in which a few Fos/type 2 NADPH-d double-labeled neurons were detected. Additionally, a large number of FG/Fos double-labeled neurons were observed to be surrounded closely by the intensive NADPH-d staining in the el of the PB. These results suggest that neurons in the el of the PB that project to the CeA are activated by visceral noxious stimulation and could be indirectly influenced by nitric oxide in the PB.

Analysis of Variance↗

PubMed2006

Activation of Group II/III metabotropic glutamate receptors attenuates LPS-induced astroglial neurotoxicity via promoting glutamate uptake.

Altered glial function that leads to oxidative stress and excitotoxicity may contribute to the initiation or progression of neuronal death in neurodegenerative diseases. We report the pivotal role of astroglial Group II and III metabotropic glutamate receptors (mGluR) against neurotoxicity. Activation of Group II or III mGluR on astrocytes with selective agonists DCG-IV or L-AP4 respectively inhibited astroglial lipopolysaccharide (LPS)-conditioned medium induced apoptosis of primary cultured mesencephalic neurons. Specific Group II or III mGluR antagonists APICA or MSOP completely abolished the neuroprotective effects of DCG-IV and L-AP4. Morphologic analysis showed that DCG-IV or L-AP4 could also attenuate the astroglial neurotoxicity to dopaminergic neurons. Measurement of extracellular glutamate concentration and [(3)H]-glutamate uptake showed that the restoration of glutamate uptake capability in LPS-treated astrocytes might be involved in the neuroprotective effects of activating astroglial Group II or III mGluR. Furthermore, we found that the repression of astroglial uptake function could be revived by GSH, and both Group II and III mGluR agonists could recover the endogenous reduced glutathione (GSH) level in LPS-treated astrocytes. These results suggested that the possible mechanisms of neuroprotection by either Type II or Type III mGluR activation may involve restoration of endogenous GSH, in turn affording recovery of astroglial capability to take up glutamate.

Animals↗

PubMed2006

Self-organization of chaos synchronization and pattern formation in coupled chaotic oscillators.

Pattern formation in spatiotemporal chaotic systems is investigated. Temporally chaotic and spatially ordered patterns are observed by varying the coupling strength. Spatial orderings emerge spontaneously due to self-organization of partial and nonlocal chaos synchronization, governed by various types of spatial symmetries. The first and secondary bifurcations from spatially disordered chaos to chaos with different levels of spatial orderings are observed and the scaling behaviors associated with these bifurcations are statistically analyzed.

Journal Article↗

PubMed2006

Novel allosteric properties produced by residue substitutions in the subunit interface of yeast NAD+-specific isocitrate dehydrogenase.

Yeast NAD+-specific isocitrate dehydrogenase (IDH) is an octamer of four IDH1 and four IDH2 subunits, and the basic structural unit of the enzyme is an IDH1/IDH2 heterodimer. To investigate one aspect of the interaction between IDH1 and IDH2, residues in a hydrophobic region at the heterodimer interface (Val-216, Ser-220, and Val-224 in IDH1; Ile-221, Val-225, and Val-229 in IDH2) were replaced by alanine residues in each and in both subunits. Gel filtration and sedimentation velocity analyses demonstrated that the residue substitutions do not disrupt the octameric structure of IDH. However, these substitutions produce novel kinetic properties including, with respect to cofactor, positive allosteric regulation by AMP and cooperativity in the absence of AMP. These allosteric properties are also apparent in NAD+-binding experiments. Despite substantial measurable activity for the mutant enzyme containing residue substitutions in both subunits, expression of this enzyme produces growth phenotypes indicative of IDH dysfunction in vivo.

Amino Acid Sequence↗

PubMed2006

Iptakalim modulates ATP-sensitive K(+) channels in dopamine neurons from rat substantia nigra pars compacta.

Iptakalim, a novel cardiovascular ATP-sensitive K(+) (K(ATP)) channel opener, exerts neuroprotective effects on dopaminergic (DA) neurons against metabolic stress-induced neurotoxicity, but the mechanisms are largely unknown. Here, we examined the effects of iptakalim on functional K(ATP) channels in the plasma membrane (pm) and mitochondrial membrane using patch-clamp and fluorescence-imaging techniques. In identified DA neurons acutely dissociated from rat substantia nigra pars compacta (SNc), both the mitochondrial metabolic inhibitor rotenone and the sulfonylurea receptor subtype (SUR) 1-selective K(ATP) channel opener (KCO) diazoxide induced neuronal hyperpolarization and abolished action potential firing, but the SUR2B-selective KCO cromakalim exerted little effect, suggesting that functional K(ATP) channels in rat SNc DA neurons are mainly composed of SUR1. Immunocytochemical staining showed a SUR1-rather than a SUR2B-positive reaction in most dissociated DA neurons. At concentrations between 3 and 300 microM, iptakalim failed to hyperpolarize DA neurons; however, 300 microM iptakalim increased neuronal firing. In addition, iptakalim restored DA neuronal firing during rotenone-induced hyperpolarization and suppressed rotenone-induced outward current, suggesting that high concentrations of iptakalim close neuronal K(ATP) channels. Furthermore, in human embryonic kidney 293 cells, iptakalim (300-500 microM) closed diazoxide-induced Kir6.2/SUR1 K(ATP) channels, which were heterologously expressed. In rhodamine-123-preloaded DA neurons, iptakalim neither depolarized mitochondrial membrane nor prevented rotenone-induced mitochondrial depolarization. These data indicate that iptakalim is not a K(ATP) channel opener in rat SNc DA neurons; instead, iptakalim is a pm-K(ATP) channel closer at high concentrations. These effects of iptakalim stimulate further pharmacological investigation and the development of possible therapeutic applications.

ATP-Binding Cassette Transporters↗

PubMed2006

Aquaporin-4 knockout regulated cocaine-induced behavior and neurochemical changes in mice.

Aquaporin-4 (AQP4) is the predominant water channel of brain, which mediates transmembrane water movement at the blood-brain barrier and at the brain-cerebrospinal fluid interface. It has been reported that AQP4 deletion results in an increase of amino acid and monoamine levels in some brain regions of mice, suggesting that AQP4 may participate in region-specific alterations in brain amino acid and monoamine metabolism. In the present study, we examined whether AQP4 affects neurotransmission in acute and chronic cocaine exposure mice. For this purpose, both wild-type and AQP4 knockout mice were used with locomotor activity evaluation and microdialysis methods. The results reveal that AQP4 deletion attenuated locomotor activity in acute and repeated cocaine exposure mice, and induced a decrease of extracellular dopamine and glutamate levels in the nucleus accumbens (NAc), a brain region known to be critically involved in the addictive properties of cocaine. Therefore, AQP4 may play a role in regulating extracellular cocaine-induced dopamine and glutamate release in the brain reward center, and in turn AQP4 deletion may attenuate cocaine reinforcement and dependence.

Animals↗

PubMed2006

Suppression of Winfree turbulence under weak spatiotemporal perturbation.

Winfree turbulence is a chaotic wave pattern developing through negative-tension instability of scroll wave filaments in three-dimensional weak excitable media. Here, we investigate the response of Winfree turbulence to a spatiotemporal forcing in the form of a traveling-wave modulation of the medium excitability. It is shown that turbulent waves can be suppressed much more rapidly by this method, in comparison with the space-uniform modulation of the medium excitability. Since the occurrence of Winfree turbulence is currently regarded as one of the possible mechanisms underlying cardiac fibrillation, this method turns out to be suggestive of a possible low-amplitude defibrillation approach.

Journal Article↗

PubMed2006

Iptakalim alleviated the increase of extracellular dopamine and glutamate induced by 1-methyl-4-phenylpyridinium ion in rat striatum.

The present study examined the effect of iptakalim (Ipt), a novel ATP-sensitive potassium (K(ATP)) channel opener (KCO), on 1-methyl-4-phenylpyridinium ion (MPP(+))-induced dopamine (DA) and glutamate efflux in extracellular fluid of rat striatum, using microdialysis technique. Rats were implanted guide cannula in the striatum and artificial cerebrospinal fluid was infused through a microdialysis probe to detect the level of DA and glutamate in the striatum. MPP(+) significantly enhanced the extracellular levels of DA and its metabolites, DOPAC and HVA, as well as glutamate. Application of Ipt (1, 10, 100 microM) concentration-dependently suppressed DA and its metabolites efflux induced by MPP(+). Concomitantly, Ipt reduced the increase of extracellular glutamate induced by MPP(+). These results suggest that Ipt can regulate DA and glutamate efflux induced by MPP(+) in rat striatum.

1-Methyl-4-phenylpyridinium↗

PubMed2006

Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28,838 middle-aged men and women.

AIMS: Serum gamma-glutamyltransferase (GGT) concentration may be involved in atherosclerosis. This study examined if serum GGT predicted coronary heart disease (CHD), especially differentiating non-fatal myocardial infarction (MI) and fatal CHD event, among the general population or participants with type-2 diabetes. METHODS AND RESULTS: A prospective study of 28,838 Finnish men and women aged 25-74 years was performed (1467 incident CHD cases; a median follow-up time of 11.9 years). Serum GGT cutpoints were the 25th, 50th, 75th, and 90th sex-specific percentiles. After adjustment for known cardiovascular risk factors, compared with the lowest GGT category, hazard ratios (HR) were 1.15, 1.25, 1.27, and 1.57 among men and 1.03, 1.22, 1.32, and 1.44 among women in other four GGT categories (P for trend <0.01, respectively). However, stronger associations were observed among subjects aged <60 and among alcohol drinkers. The strength of association was similar for non-fatal MI and for fatal CHD. Among subjects with type-2 diabetes, the corresponding adjusted HRs were 1.29, 1.57, 1.88, and 1.78 (P trend=0.03, men and women combined). CONCLUSION: This study suggests an independent mechanism linking serum GGT to CHD among general population. Even though the strength of association appeared to be modest among all subjects, stronger associations were observed among subjects aged <60 and among alcohol drinkers. Especially, measurement of serum GGT among type-2 diabetics may be helpful to predict the future risk of CHD.

Adult↗

PubMed2006

How well does the metabolic syndrome defined by five definitions predict incident diabetes and incident coronary heart disease in a Chinese population?

We evaluate the ability of the metabolic syndrome (MetS) defined by five definitions for predicting both incident CHD and diabetes combined, diabetes alone, and CHD alone in a Chinese population. The screening survey for type 2 diabetes was conducted in 1994. A follow-up study of 541 high-risk non-diabetic individuals who were free of CHD at baseline was carried out in 1999 in Beijing area. The MetS was defined by the World Health Organization (WHO), European Group for the Study of Insulin Resistance (EGIR), American College of Endocrinology (ACE), the International Diabetes Federation (IDF), and the National Cholesterol Education Program and the American Heart Association (AHA) (updated NCEP) criteria. From a multiple logistic regression adjusting for age, sex, education, occupation, smoking, family history of diabetes, and total cholesterol, the relative risk of the ACE-defined MetS for incident diabetes alone (67 cases) was 2.29 (95% CI, 1.20-4.34). The MetS defined by the five definitions was associated with a 1.8-3.9 times increased risk for both incident CHD and diabetes combined (59 cases), and with a 1.9-3.0 times for total incident diabetes (126 cases). None of the five definitions predicted either incident CHD alone (177 cases) or total incident CHD (236 cases). In conclusion, the MetS defined by the current definitions appears to be more effective at predicting incident diabetes.

Adult↗

PubMed2006

Sporadic feedback control of flow turbulence.

In this work we consider the problem of flow turbulence control in a two-dimensional Navier-Stokes equation. We suggest a control strategy which sporadically applies global feedback to a single velocity component of the velocity field. It is found that this control strategy can significantly enhance the control efficiency when the optimal fraction for the control period is suitably chosen, both larger and smaller control time fractions may reduce the control precision. The physical mechanism underlying this interesting and strange behavior is heuristically analyzed, based on mode-mode interactions.

Journal Article↗

PubMed2006

Controlling drift-wave turbulence using time-delay and space-shift autosynchronization feedback.

Drift-wave turbulence control in a one-dimensional nonlinear drift-wave equation driven by a sinusoidal wave is considered. We apply time-delay and space-shift feedback signals, to suppress turbulence. By using global and local pinning strategies, we show numerically that the turbulent state can be controlled to periodic states effectively if appropriate time-delay length and space-shift distance are chosen. The physical mechanism of the control scheme is understood based on the energy-minimum principle.

Journal Article↗

PubMed2006

Iptakalim inhibits nicotine-induced enhancement of extracellular dopamine and glutamate levels in the nucleus accumbens of rats.

Iptakalim (Ipt) is a novel ATP-sensitive potassium channel opener. It has been reported that Ipt inhibited cocaine-induced dopamine and glutamate release, suggesting that Ipt may regulate drug addiction. Recently, we found that Ipt blocked nicotinic acetylcholine receptor (nAChR)-mediated currents in a heterologously expressed SH-EP1 cell line and in native midbrain dopamine neurons. In the present study, we examined whether Ipt prevents nicotine-induced neurotransmitter release in the nucleus accumbens (NAc) using in vivo microdialysis methods in awake, freely moving rats. Ipt was administered through a microdialysis probe, following systemic administration of nicotine (0.5 mg/kg, s.c.). The results show that acute nicotine treatment induced an increase of both dopamine and glutamate levels in the rat NAc, and that Ipt significantly attenuated nicotine's effects in a concentration-dependent manner. Therefore, Ipt may serve as a novel compound to block nicotine-induced dopamine and glutamate release in the brain reward center, in turn decreasing nicotine reinforcement and dependence.

Analysis of Variance↗

PubMed2006

Physiological consequences of loss of allosteric activation of yeast NAD+-specific isocitrate dehydrogenase.

Based on allosteric regulatory properties, NAD+-specific isocitrate dehydrogenase (IDH) is believed to control flux through the tricarboxylic acid cycle in vivo. To distinguish growth phenotypes associated with regulatory dysfunction of this enzyme in Saccharomyces cerevisiae, we analyzed strains expressing well defined mutant forms of IDH or a non-allosteric bacterial NAD+-specific isocitrate dehydrogenase (IDHa). As previously reported, expression of mutant forms of IDH with severe catalytic defects but intact regulatory properties produced an inability to grow with acetate as the carbon source and a dramatic increase in the frequency of generation of petite colonies, phenotypes also exhibited by a strain (idh1Deltaidh2Delta) lacking IDH. Reduced growth rates on acetate medium were also observed with expression of enzymes with severe regulatory defects or of the bacterial IDHa enzyme, suggesting that allosteric regulation is also important for optimal growth on this carbon source. However, expression of IDHa produced no effect on petite frequency, suggesting that the intermediate petite frequencies observed for strains expressing regulatory mutant forms of IDH are likely to correlate with the slight reductions in catalytic efficiency observed for these enzymes. Finally, rates of increase in oxygen consumption were measured during culture shifts from medium with glucose to medium with ethanol as the carbon source. Strains expressing wild-type or catalytically deficient mutant forms of IDH exhibited rapid respiratory transitions, whereas strains expressing regulatory mutant forms of IDH or the bacterial IDHa enzyme exhibited much slower respiratory transitions. This suggests an important physiological role for allosteric activation of IDH during changes in environmental conditions.

Allosteric Site↗

PubMed2006

Effects of systemic administration of iptakalim on extracellular neurotransmitter levels in the striatum of unilateral 6-hydroxydopamine-lesioned rats.

The function of ATP-sensitive potassium (KATP) channels in nigrostriatal pathway in Parkinson's disease (PD) was studied by employing a novel KATP channel opener iptakalim (Ipt). Apomorphine-induced rotation behavior test and microdialysis experiment were carried out in unilateral 6-hydroxydopamine (6-OHDA) lesioned rats. Behavior test showed that systemic administration of Ipt failed to significantly alleviate apomorphine-induced rotation in unilateral 6-OHDA-lesioned PD model rats. However, using in vivo microdialysis in this PD model rats, it was found that Ipt could increase extracellular dopamine levels in the lesioned side of the striatum and decrease dopamine levels in the intact side of the striatum. Meanwhile, Ipt had no influence on glutamate levels in the intact side, but it did decrease glutamate levels in the lesioned side of the striatum of PD rats. Additionally, in primary cultured rat astrocytes, 6-OHDA decreased overall glutamate uptake activity, but this decrease was recovered and glutamate uptake activity was restored by the opening of KATP channels induced by Ipt and pinacidil. The classical KATP channel blocker glibenclamide completely abolished the effects of Ipt and pinacidil. The present study suggests that (i) the function of KATP channels in the lesioned and intact nigrostriatal pathway is different in unilateral 6-OHDA-lesioned PD model rats. (ii) KATP channels regulate extracellular neurotransmitter levels in the striatum of unilateral 6-OHDA-lesioned rats and may play neuroprotective roles due to their effects on glutamate transporters.

Adenosine Triphosphate↗

PubMed2006

Screen-detected diabetes, hypertension and hypercholesterolemia as predictors of cardiovascular mortality in five populations of Asian origin: the DECODA study.

BACKGROUND: The World Health Organization (WHO) predicts that the Asia Pacific region will experience an increase in cardiovascular disease (CVD) as a result of demographic changes and an increasing prevalence of diabetes. The aims of this study were to assess the predictive value of glucose tolerance status as a risk factor for CVD and identify a high-risk group for fatal CVD in population-based studies of Asians. DESIGN: A meta-analysis of five prospective cohort studies of Japanese and Asian Indian origin from five countries. METHODS: A total of 6573 subjects without a history of CVD from five prospective studies were followed for 5-10 years. Diabetes at baseline was diagnosed according to 1999 WHO criteria. Hazard ratios for death from CVD were estimated using a Cox proportional hazard model, adjusting for glucose tolerance status together with established risk factors for CVD. RESULTS: The meta-analysis showed that the overall hazard ratios (95% confidence interval) for CVD mortality corresponding to the presence of screen-detected diabetes, hypertension and hypercholesteremia were 3.42 (2.23-5.23), 1.57 (1.10-2.24) and 1.49 (1.05-2.10), respectively. Stratified multivariate analysis of the pooled data showed that subjects with screen-detected diabetes in the presence of hypertension or hypercholesteremia had the highest risk of CVD in individuals without previous CVD or diabetes. Subjects with screen-detected diabetes in the presence of hypertension or hypercholesteremia comprised 78% of CVD deaths that occurred in all subjects with screen-detected diabetes. CONCLUSIONS: The early detection of undiagnosed diabetes in hypertension or hypercholesteremia may have clinical and public health implications for the primary prevention of rapidly increasing diabetes-related atherosclerotic CVD in Asian populations.

Asia↗

PubMed2006

Role of 11-beta-hydroxysteroid dehydrogenase type 1 in differentiation of 3T3-L1 cells and in rats with diet-induced obesity.

AIM: To observe the roles of 11-beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in in vitro preadipocyte differentiation and in rats with diet-induced obesity (DIO). METHODS: Protein expression of 11beta-HSD1 in the process of 3T3-L1 cell differentiation and in various tissues of the rats were detected by Western blot analysis; expression of 11beta-HSD1 mRNA and glucocorticoid receptor (GR) and other marker genes of preadipocyte differentiation were detected by using real-time PCR. RESULTS: Lipid droplets in 3T3-L1 cells accumulated and increased after stimulation. A dramatically elevated protein level of 11beta-HSD1, especially in the late stages of 3T3-L1 cell differentiation, was detected. The relative mRNA levels of 11beta-HSD1, GR and cell differentiation markers LPL, aP2, and FAS were upregulated, and Pref-1 was downregulated during the differentiation. In DIO rats, bodyweight, visceral adipose mass index and the protein expression of 11beta-HSD1 increased, especially in adipose tissue, brain and muscles. Serum insulin, triglyceride, total cholesterol and low-density lipoprotein cholesterol were found to be increased in DIO rats, but without any obvious changes in blood glucose or tumor necrosis factor-alpha levels. CONCLUSION: 11beta-HSD1 may promote preadipocyte differentiation, and may be involved in the development of obesity.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗